The present invention relates to a method of preparation of a tin-polyphosphate complex intended to be labelled with 99m Technetium for medical diagnosis by scintigraphy, especially bone scintigraphy.
The invention also relates to a medical diagnosis kit which contains, in a single bottle or flask, the elements to be used in scintigraphy, after labelling thereof.
99M Technetium is endowed with properties which are highly looked for in the medical field, in particular as regards bone scintigraphy and the detection of bone cancerous humors.
In addition to the fact that it can readily be obtained from 99 Mo, this substance has a high quality radiation, a .gamma.-radiation energy of 140 keV and a short half-life of 6 hours with no emission of .beta.-rays.
Furthermore, said substance makes it possible to associate a highly-accurate diagnosis with an acceptable, easily employed, dose for the patient.
99M Tc is commonly used for examining various organs such as the thyroid gland, the brain, the liver, the splean, the kidvens and the reticulo-endothelial system. To this end, this substance is incorporated into the body in association with a vehicular compound, chosen in view of its tropism and of its particular biological properties.
According to recent researches, it is known to use polyphosphates labelled with 99m Tc in the field of scintigraphy. Some of these polyphosphates, e.g. triphosphate, as well as some polyphosphates having a molecular weight of 4 500 give excellent results, but such is not the case with the diacidic phosphate and with fluorophosphate which are characterized by poor tropism.
The labelling of these substances, is conventionally accomplished by adding to a pertechnetate solution a freshly prepared solution of stannous chloride in a diluted hydrochloric medium, stirring the mixture for 3 to 5 minutes, adding a polyphosphate solution, stirring thoroughly, adjusting the pH to approximately 7.5 by means of a sodium hydroxide or sodium bicarbonate solution, finally sterilizing the preparation by filtering the latter through a 0.22 .mu. filtering membrane in a pre-sterilized empty bottle.
Labeling methods of this type have the disadvantages of being complex, of providing a composition which does not keep well and requires at the moment of use a large number of operating steps which, quite often, cannot be readily performed or even cannot be carried out at all, prior to injection into the patient. For instance, freshly prepared stannous chloride is not always available, and the numerous successive operating steps, involving adding reagents, stirring and adjusting pH-values, complicate the preparations which are required for the medical diagnosis procedure.
Moreover, prior researches on the Tc99 labelling of polyphosphates suggested that the effective substances were essentially large molecules having a very high molecular weight (above 1,500), such as mentioned e.g. in G. Subramanian's works (99mTc polyphosphate PP 46 : A new radio-pharmaceutical for skeletal imaging, Upstate Medical Centre, Syracuse N.Y., 16th Session, June 1971). Indeed, whereas monophosphate had provided but poor results, triphosphate had brought a marked improvement since it was better fixed to the bones and more chemically stable. The natural tendency appeared to lead to polyphosphates of high molecular weight, containing many phosphorous atoms in their chain.
On the other hand, the implication was left that pyrophosphate (P.sub.2 O.sub.7 Na.sub.4) might not be used as a valuable vehicular substance for Tc99 at the level of the skeleton, in view of the rapid hydrolysis thereof by pyrophosphatases.